The Ia alloantigens are the only isolated gene products of the immune response control region (I region) of the mouse major histocompatibility complex (MHC). The molecules bearing Ia alloantigenic determinants have been implicated in the control of immune response function by experiments showing that anti-Ia alloantisera specifically inhibit such functions. Furthermore, the Ia structural genes are arranged so that the Ia molecules could provide a molecular explanation for Ia gene complementation effects. Since Ia antigens may have an active role in the control of immune response, these molecules must be analyzed to see whether their structural features can explain how they carry out their proposed function. The research projected here includes structural, genetic and serological investigation of Ia molecules. Structural analysis will include assessment of variability in primary structure, primarily by peptide mapping, localization of antigenic sites, search for interaction with other cell proteins and mechanism of assembly and transport of Ia molecules to the cell surface. Genetic analysis will include a survey of recombinants and mutants to identify features of Ia molecules important to function.